Submissions for variant NM_002180.2(IGHMBP2):c.1813C>T (p.Arg605Ter) (rs991227431)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000578618	SCV000680530	pathogenic	not provided	2017-02-24	criteria provided, single submitter	clinical testing	The R605X nonsense variant in the IGHMBP2 gene has been reported previously in association with SMARD1 (Grohmann et al., 2003). R605X is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
Inherited Neuropathy Consortium	RCV000790272	SCV000929675	uncertain significance	Distal spinal muscular atrophy		no assertion criteria provided	literature only
Invitae	RCV000642633	SCV000764320	pathogenic	Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S	2017-09-17	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg605*) in the IGHMBP2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with autosomal recessive spinal muscular atrophy with respiratory distress type 1 (PMID: 14681881) and Charcot-Marie Tooth disease type 2 (PMID: 25439726). Loss-of-function variants in IGHMBP2 are known to be pathogenic (PMID: 14681881, 25439726, 25568292). For these reasons, this variant has been classified as Pathogenic.